Alkylation of toluene or phenol is a typical Friedel-Crafts reaction that is important in industry due to the wide application of the alkylated products. Among the alkylated isomers, the para-counterpart such as para-alkylated toluene or phenol is highly desirable for industrial applications as essential feedstock for antioxidants, phenolic resins, ultraviolet absorbers, varnishes and heat stabilizers in polyolefins. P. Elavarasan, K. Kondamudi, S. Upadhyayula, Chem. Eng. 1 2011, 166, 340-347. 4-tert-butylphenol is used to make oils and phosphate esters. F. M. Moghaddam, M. Akhlaghi, L. Hojabri, M. G. Dekamin, Trans. C Chem. Chem. Eng. 2009, 16, 81-88. Thus, efficient and selective alkylation, to yield para-substituted alkyl aromatics has received tremendous interest in recent years. P. Lu, Z. Fei, L. Li, X. Feng, W. Ji, W. Ding, Y. Chen, W. Yang, Z. Xie, Appl. Catal., A 2013, 453, 302-309.
In the course of more than 100 years of Friedel-Crafts chemistry, considerable work has been done on aromatic alkylations utilizing Friedel-Crafts chemistry. G. A. Olah, Friedel-Crafts Chemistry; Wiley-Interscience: New York, 1973. Olah and coworkers reported Friedel-Crafts alkylation of anisole and toluene using metal halides such as AlCl3 and BF3. G. A. Olah, J. A. Olah, T. Ohyama, J. Am. Chem. Soc. 1984, 106, 5284-5290. The same group subsequently reported boron, aluminum, and gallium triflates as convenient and effective new Friedel-Crafts catalysts for alkylation of benzene and toluene. G. A. Olah, O. Farooq, S. M. F. Farnia, J. A. Olah, J. Am. Chem. Soc. 1988, 110, 2560-2565. However, the para-selectivity was poor due to rapid isomerization to a more thermodynamically favored meta isomer. Brown et al. obtained 10% meta substitution in methylation (C. R. Smoot, H. C. Brown, J. Am. Chem. Soc. 1956, 78, 6249-6254), 21% in ethylation (L. M. Stock, H. C. Brown, J. Am. Chem. Soc. 1960, 82, 1942-1947), 27% in isopropylation (H. C. Brown, H. Jungk, J. Am. Chem. Soc. 1955, 77, 5584-5589), 32% in tert-butylation (H. Jungk, C. R. Smoot, H. C. Brown, J. Am. Chem. Soc. 1956, 78, 2185-2190), and 21% in benzylation (H. C. Brown, C. R. Smoot, J. Am. Chem. Soc. 1956, 78, 6255-6259) in Friedel-Crafts alkylations of toluene. Gold and Riley reported the 60% perchloric acid catalyzed alkylation of anisole with alcohols and observed 45% ortho- and 55% para-alkylation with isopropyl alcohol and 20% ortho- and 80% para-alkylation with tent-butyl alcohol. V. Gold, T. Riley, J. Chem. Soc. 1962, 4183-4188. Kovacic and Hiller reported that alkylation of anisole with tert-butyl chloride (t-BuCl) gave 6% meta and 94% para isomer. P. Kovacic, J. J. Hiller, J. Org. Chem. 1965, 30, 1581-1588. Stang and Anderson studied the alkylation with vinyl triflates in the presence of a sterically hindered non-nucleophilic base 2,6-di-tert-butyl-4-methylpyridine producing 11% ortho and 89% para isomer for anisole alkylation and 28% ortho, 8% meta and 64% para isomer for toluene. P. J. Stang, A. G. Anderson, J. Am. Chem. Soc. 1978, 100, 1520-1525. Thus, it has been difficult to achieve high conversion retaining high para selectivity during alkylation of toluene and phenol. EtAlCl2 has been employed in cycloalkylation of benzene (R. Wolovsky, N. Maoz, Z. Nir, Synthesis 1970, 656-657) and alkylation of substituted arenes, but only in polar solvents such as dichloromethane (D. Chaturvedi, A. K. Chaturvedi, N. Mishra, V. Mishra, Org. Biomol. Chem. 2012, 10, 9148-9151).
There remains a need for Friedel-Crafts methods exhibiting high regioselectivity and conversion.